702 Randomized phase III trial comparing 5FU bolus and low dose leucovorin versus 5FU bolus plus continuous 5FU infusion and high dose LV in metastatic colorectal cancer

Abstract

Monthly 5 day course of 5FU bolus infusion with low dose Leucovorin (FUFOL 1d) has the best therapeutic index for 5FU modulation in metastatic colorectal cancer. Delivering 5FU protracted continuous infusion has also a better index than 5FU bolus. The bi-monthly combination of 5FU bolus followed by 5FU continuous infusion and high dose (LV 5FU2) has show a good efficacy with low toxicity in several phase II studies. The current study compares FUFOLId and LV 5FU2. From March 1991 until April 1994, 437 patients (pts), stratified according to performance status, presence of measurable disease, and synchroneous or metachroneous disease, were randomized to (A) FUFOLld: IV bolus 5FU 425 mg/m2 d1-5 with folinic acid 20 mg/m2 IV d1-5 q 4 wk or (B) LV 5FU2: folinic acid 200 mg/m2 2-hour infusion followed by IV bolus 5FU 400 mg/m2 and 22-hour infusion FU 600 mg/m2 d1-2 q 2 wk. Therapy was continued until disease progression and second-line chemotherapy including 5FU continuous infusion was allowed in both arms. Response rate (306 evaluable pts), progressionfree survival (PFS) and overall survival (OS) are as follows: Treatment Pts Response Pts PFS (wk) OS (wk) FUFOL1d 147 17% 218 22.8 57.2 LVSFU2 159 34% 219 29.5 61.4 P = 0.002 P = 0.008 P = 0.006 41 pts (21.5%) experienced grade 3–4 toxicities in arm A versus 18 pts (9.2%) in arm B, P = 0.0004. grade 3–4 toxicities (%) were in arm A: neutrophils 7.9 platelets 1, nausea 2.6, diarrhea 4.7, mucositis 9.9, alopecia I, skin 0.5 and in arm B: neutrophils 2, platelets 0.5, nausea 3.1, mucositis 1.5, alopecia 0.5, skin 0.5. Treatment was stopped in one patient in arm A and 3 in arm B who experienced angina pectoris. We conclude that the bi-monthly combination of 5FU bolus and continuous infusion with high-dose folinic acid is more active and less toxic than monthly 5 day course of bolus 5FU with low dose Leucovorin.